1H-NMR spectra enabled us to determine the fermented metabolites excreted by the parasites during their in vitro culture. The final products of glucose catabolism in Leishmania are usually CO2, succinate, acetate, L-lactate, pyruvate, L-alanine, and ethanol [17]. As with T. cruzi [18], Bortezomib clinical one of the major metabolites excreted by Leishmania spp. is succinate, with the main role likely to be to maintain the glycosomal redox balance by providing two glycosomal oxidoreductase enzymes. These enzymes allow reoxidation of NADH produced by glyceraldehyde-3-phosphate dehydrogenase in the glycolytic pathway. Succinic fermentation offers one significant advantage as it requires only half the produced phosphoenolpyruvate (PEP) to maintain the NAD+/NADH balance.

The remaining PEP is converted to acetate, depending on the species under consideration.The majority of metabolites excreted by L. infantum are succinate and acetate. In the case of L. infantum, variations in the final catabolism products seem to be dependent on the structural aspects of the compounds assayed. These data agree well with those of other authors [18].Analyses of in vitro and in vivo results of Trypanosoma cruzi showed that the best potential flavonoids to treat Chagas disease were the acetylated compounds 2, 5, and 6 [15]. The present work confirmed this conclusion in the case of visceral leishmaniasis (L. infantum) and mucocutaneous leishmaniasis (L. braziliensis). Moreover, these data are consistent with others previously published, which showed that several acetylated flavonoids derived from Consolida oliveriana were very active in vitro against both extracellular and intracellular forms of L.

(V.) peruviana and L. (V.) braziliensis [9].In conclusion, this study has demonstrated that flavonoid derivatives are active against L. infantum and L. braziliensis. These results support further investigation of flavonoid compounds as potential agents against Leishmaniasis.AcknowledgmentsThe authors would like to express their thanks to M. J. Mart��nez-Guerrero, J. Laz��en-Alc��n and E. Onorato-Guti��rrez for their expert technical help in transmission electron microscopy, flow cytometry and nuclear magnetic resonance spectroscopy, respectively. They also appreciate the help of E. Guerrero L��pez and C. Anaya Romero in culture media preparation Cilengitide and in vitro culture. This work was financially supported by the Consolider Ingenio Project CSD2010-00065 (Spain).
Multiple tropopauses (MTs) are structures that regularly recur in the midlatitudes [1�C3] and are extremely important for stratosphere-troposphere exchange (STE).